WO2006018853A2 - Nouveaux polymorphes d'efavirenz - Google Patents

Nouveaux polymorphes d'efavirenz Download PDF

Info

Publication number
WO2006018853A2
WO2006018853A2 PCT/IN2004/000250 IN2004000250W WO2006018853A2 WO 2006018853 A2 WO2006018853 A2 WO 2006018853A2 IN 2004000250 W IN2004000250 W IN 2004000250W WO 2006018853 A2 WO2006018853 A2 WO 2006018853A2
Authority
WO
WIPO (PCT)
Prior art keywords
efavirenz
process according
drying
solvent
carried out
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/IN2004/000250
Other languages
English (en)
Other versions
WO2006018853A3 (fr
Inventor
Bandi Parthasaradhi Reddy
Kura Rathnakar Reddy
Rapolu Raji Reddy
Dasari Muralidhara Reddy
Kesireddy Subash Chander Reddy
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hetero Drugs Ltd
Original Assignee
Hetero Drugs Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hetero Drugs Ltd filed Critical Hetero Drugs Ltd
Priority to US10/568,904 priority Critical patent/US20060235008A1/en
Priority to PCT/IN2004/000250 priority patent/WO2006018853A2/fr
Publication of WO2006018853A2 publication Critical patent/WO2006018853A2/fr
Anticipated expiration legal-status Critical
Publication of WO2006018853A3 publication Critical patent/WO2006018853A3/fr
Priority to US13/174,893 priority patent/US8242267B2/en
Priority to US13/540,987 priority patent/US8466279B2/en
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
    • C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
    • C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D265/18—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in position 2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV

Definitions

  • the present invention relates to novel polymorphs of efavirenz, processes for their preparation and pharmaceutical compositions containing them.
  • the present invention relates to novel polymorphs of efavirenz, processes for their preparation and pharmaceutical compositions containing them.
  • This compound is used for the preparation of a medicament having nonnucleoside HIV-1 reverse transcriptase inhibiting activity that is useful in the prevention or treatment of infection by HIV and the treatment of AIDS.
  • Efavirenz is sold commercially as SUSTIVA® by Bristol Myers Squibb.
  • WO patent application publication No. 98/33782 disclosed three crystalline forms, Form I (characterized by an x-ray powder diffraction patterns having peaks expressed as 2 ⁇ at 6.1 , 6.4, 10.4, 10.9, 12.3, 13.2, 14.2, 15.2, 16.9, 18.4, 19.2, 20.1 , 21.2, 22.3, 23.0, 24.9, 25.9, 26.3, 27.2, 28.1 , 28.6, 29.1 , 29.5, 30.7, 32.4 and 38.3 degrees), Form Il (characterized by an x-ray powder diffraction patterns having peaks expressed as 2 ⁇ at 3.6, 6.3, 11.1 , 12.8, 13.3, 14.3, 16.1, 16.9, 18.5, 19.2, 19.6, 20.6, 21.3, 22.6, 23.2, 24.4, 24.9, 26.0, 26.8, 27.6, 28.4, 29.2, 29.6, 30.6, 31.9 and 33.8 degrees) and Form III (characterized by an x-ray powder diffraction patterns having peaks expressed as 2 ⁇ at 7.2, 10.9, 13.7, 14.
  • WO patent application publication No. 99/64405 disclosed fivs crystalline forms, Form 1 (characterized by an x-ray powder diffraction patterns having peaks expressed as 26 at about 6.0, 6.3, 10.3, 10.8, 14.1 , 16.8, 20.0, 20.5, 21.1 and 24.8 degrees), Form 2 (characterized by an x-ray powder diffraction patterns having peaks expressed as 26 at about 6.8, 9.2, 12.3, 16.2, 21.4, 22.7, 24.1 and 28.0 degrees), Form 3 (characterized by an x-ray powder diffraction patterns having peaks expressed as 26 at about 7.1 , 7.3, 11.0, 13.8, 20.9, 23.3, 27.9 and 33.5 degrees), Form 4 (characterized by an x-ray powder diffraction patterns having peaks expressed as 26 at about 3.6, 6.3, 9.7, 11.0, 12.7, 13.2, 16.1, 19:2 " , 19.5/20.6 and 24.3 degrees) and Form 5 (characterized by an x-ray powder diffraction patterns having peaks expressed as 26 at about 10.2, 11.4,
  • the novel form is at least as stable as the reported forms (Form I, Form II, Form III, Form 1 , Form 2, Form 3, Form 4 and Form 5).
  • the novel crystalline form is stable over the time and has good flow properties and so, the novel crystalline form is suitable for formulating efavirenz.
  • Amorphous form of efavirenz has not been reported in the prior art. So, there is a need for stable amorphous form of efavirenz for better pharmaceutical preparations.
  • One object of the present invention is to provide a stable novel crystalline form of efavirenz, process for preparing it and a pharmaceutical composition containing it.
  • Another object of the present invention is to provide a novel stable amorphous form of efavirenz, process for preparing it and a pharmaceutical composition containing it.
  • DETAILED DESCRIPTION OF THE IMVEMTION there is provided a novel amorphous form of efavirenz.
  • the amorphous efavirenz is characterized by having broad x-ray diffraction spectrum as in figure 1.
  • a process for preparation of amorphous efavirenz which comprises: a) precipitating from a solution of efavirenz in a C 3 - C 8 -ketonic solvent by using water as precipitating solvent at below about 15 0 C, and collecting the precipitated solid; and b) drying the solid collected at about 40 0 C - 65 0 C to obtain amorphous efavirenz.
  • the preferable ketonic solvent is selected from acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl tert-butyl ketone and diethyl ketone; more preferable ketonic solvent is selected from acetone and diethyl ketone; and still more preferable ketonic solvent is acetone.
  • the solution of efavirenz in the ketonic solvent may be prepared by dissolving efavirenz in a known form or in crystalline form H1 described below in ths said ketonic solvent.
  • crude efavirenz may also be used in the process.
  • the precipitation is carried out at about O 0 C - 10 0 C and more preferably at about 2 0 C - 5 0 C.
  • the precipitated solid may be collected by filtration or centrifugation.
  • the preferable temperature range of drying is at about 50 0 C - 60 0 C and more preferable temperature range is at about 55 0 C - 60 0 C.
  • the process is carried out by precipitating from a solution of efavirenz in a C 3 - C 8 -ketonic solvent, preferably acetone, by adding the said solution to water at about O 0 C - 10 0 C and more preferably at about 2 0 C - 5 0 C; collecting the precipitated solid by filtration or centrifugation; and drying the solid collected at about 40 0 C - 65 0 C, more preferably at about 55 0 C - 60 0 C to obtain amorphous efavirenz.
  • the novel amorphous efavirenz is found to have better dissolution properties when compared with the known forms.
  • a novel crystalline form of efavirenz designated as form H1 , characterized by an x-ray powder diffraction spectrum having peaks expressed as 2 ⁇ at about 5.4, 10.4, 11.6, 12.5, 15.3, 20.1 , 20.8, 22.5, 23.1 , 25.7, 27.9, 28.5, 28.8, 29.5, 30.2 and 38.2 degrees.
  • Figure 2 shows typical form H1 x-ray powder diffraction spectrum.
  • a process for preparation of efavirenz form HI which comprises: si) precipitating from a solution of efavirenz in a C-, - CG -alcoholic, Cs - Gs - ketonic solvent or a mixture thereof by using water as precipitating solvent at below about 15 0 C, collecting the precipitated solid; b) drying the solid collected at about 25 0 C - 35 0 C until the water content falls in the range 2 - 10% of the solid by weight; and c) drying the solid obtained in (b) at about 40 0 C - 55 0 C to obtain crystalline efavirenz form H1. .
  • the preferable alcoholic solvent is selected from ethanol, n-propanol, n- butanol, isopropanol and methanol and more preferable alcoholic solvent is n- propanol. .
  • the preferable ketonic solvent is selected from acetone, methyl ethyl ketone, methyl isobutyl ketone, methyl tert-butyl ketone and diethyl ketone; more preferable ketonic solvent is selected from acetone and diethyl ketone; and still more preferable ketonic solvent is acetone.
  • the solution of efavirenz in the ketonic or alcoholic solvent may be prepared by dissolving efavirenz in a known form or in amorphous form in the said ketonic or alcoholic solvent. Alternatively, crude efavirenz may also be used in the process.
  • the precipitation is carried out at about O 0 C - 1O 0 C and more preferably at about 2 0 C - 5 0 C.
  • the precipitated solid may be collected by filtration or centrifugation. It has been found that the drying of precipitated product in step (a) directly at higher temperature leads to known crystalline form 1 (WO patent application publication No. 99/64405). Preferably the drying in step (b) is carried out until the water content falls in the range 2 - 5% of the solid by weight.
  • the preferable temperature range of drying in step (c) is at about 40 0 C - 50 0 C and more preferably at about 40 0 C - 45 0 C.
  • the process is carried out by precipitating from a solution of efaviren ⁇ in a C 1 - C 6 -alcoholic solvent, preferably n-propanol or isopropanol, C 3
  • - C 3 -ketonic solvent preferaly acetone or diethyl ketone, or a mixture thereof by adding the said solution to water at about O 0 C - 10 0 C and more preferably at about 2 0 C - 5 0 C; collecting the precipitated solid by filtration or centrifugation; drying the precipitated solid at about 25 0 C - 35 0 C until the water content is 2 - 5%; and drying the solid obtained at about 40 0 C - 55 0 C, preferably at about 40 0 C
  • alkyl portion of the C 1 to C 5 -alcohol and C 3 to C 8 -ketone used can be straight or branch, unsubstituted or substituted with for example alkoxy, halogen, nitro, cyano or hydroxy groups.
  • the novel crystalline efavirenz form H1 is at least as stable as the reported forms (Form I, Form II, Form III, Form 1 , Form 2, Form 3, Form 4 and
  • the novel crystalline form is stable over the time and has good flow properties and so, the novel crystalline form is suitable for formulating efavirenz.
  • novel polymorphs of efavirenz are useful for the preparation of medicaments having nucleoside HIV-1 reverse transcriptase inhibiting activity thpt is, useful in the. prevention or treatment of infection by HIV. and the treatment of aids.
  • the novel polymorphs of efavirenz can be used in pharmaceutical compositions generally in combination with at least one pharmaceutically acceptable excipient.
  • Figure 1 is a x-ray powder diffraction spectrum of amorphous form of efavirenz.
  • Figure 2 is a x-ray powder diffraction spectrum of efavirenz form H1.
  • x-Ray powder diffraction spectrum was measured on a Bruker axs D8 advance x-ray powder diffractometer having a copper-K ⁇ radiation.
  • Efavirenz crude (5 gm, obtained by the process described in example 6, step A to step D, of U.S. Patent No. 5,519,021) is dissolved in acetone (20 ml) at 23 0 C - 30 0 C, slowly added to water (200 ml) for 30 minutes at O 0 C - 5 0 C and stirred for 1 hour at the same temperature. Then the separated solid is filtered, washed with water (20 ml) and dried at 55 0 C - 60 0 C for 5 hours to give 4.5 gm of amorphous efavirenz.
  • Efavirenz form 1 (10 gm, obtained by the process described in example 8 of WO patent application publication No. 99/64405) is dissolved in diethylketone (50 ml) at 25 0 C - 30 0 C, slowly added to water (350 ml) for 45 minutes at O 0 C - 5 0 C and stirred for 2 hours at the same temperature. Then the separated solid is filtered, washed with water (50 ml) and dried at 55 0 C - 60 0 C for 5 hours to give 9.5 gm of amorphous efavirenz.
  • Efavirenz crude (5 gm) is dissolved in n-propanol (20 ml) at 25 0 C - 30 0 C, slowly added to water (200 ml) for 30 minutes at O 0 C - 5 0 C and stirred for 1 hour at the same temperature. Then the separated solid is filtered, washed with water (20 ml) and dried at 25 0 C - 30 0 C for 18 hours to obtain efavirenz as wet solid (moisture content: 2.5% by Karl fisher method). The wet solid is dried at 40 0 C - 45 0 C to give 4.4 gm of efavirenz form H1 (water content: 0.3%).
  • Example 4 Amorphous efavirenz (5 gm, obtained in example 1) is dissolved in isopropanol (25 ml) at 25 0 C - 30 0 C, slowly added to water (170 ml) for 30 minutes at O 0 C - 5 0 C and stirred for 1 hour.30 minutes at the same temperature. Then the separated solid is filtered,_washed with water (30 ml) and dried at 25 0 C - 30 0 C for 20 hours to obtain efavirenz as wet solid (moisture content: 3.2 % by Karl fisher method), The wet solid is dried at 40 0 C - 45 0 C to give 4.3 gm of efavirenz form H1 (water content: 0.35%).

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • AIDS & HIV (AREA)
  • General Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne de nouvelles formes amorphes et cristallines d'efavirenz, des procédés permettant leur préparation, ainsi que des compositions pharmaceutiques les contenant. Selon la présente invention, l'efavirenz brut est dissous dans l'acétone à 25 °C - 30 °C, la solution est ajoutée lentement à de l'eau pendant 30 minutes à 0 °C - 5 °C, elle est agitée pendant une heure à la même température, le solide séparé est filtré, lavé à l'eau et séché à 55 °C - 60 °C pendant cinq heures pour donner un efavirenz amorphe.
PCT/IN2004/000250 2004-08-19 2004-08-19 Nouveaux polymorphes d'efavirenz Ceased WO2006018853A2 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US10/568,904 US20060235008A1 (en) 2004-08-19 2004-08-19 Novel polymorphs of efavirenz
PCT/IN2004/000250 WO2006018853A2 (fr) 2004-08-19 2004-08-19 Nouveaux polymorphes d'efavirenz
US13/174,893 US8242267B2 (en) 2004-08-19 2011-07-01 Polymorphs of efavirenz
US13/540,987 US8466279B2 (en) 2004-08-19 2012-07-03 Polymorphs of efavirenz

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IN2004/000250 WO2006018853A2 (fr) 2004-08-19 2004-08-19 Nouveaux polymorphes d'efavirenz

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US10568904 A-371-Of-International 2004-08-19
US13/174,893 Continuation US8242267B2 (en) 2004-08-19 2011-07-01 Polymorphs of efavirenz

Publications (2)

Publication Number Publication Date
WO2006018853A2 true WO2006018853A2 (fr) 2006-02-23
WO2006018853A3 WO2006018853A3 (fr) 2008-04-10

Family

ID=35907805

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2004/000250 Ceased WO2006018853A2 (fr) 2004-08-19 2004-08-19 Nouveaux polymorphes d'efavirenz

Country Status (2)

Country Link
US (3) US20060235008A1 (fr)
WO (1) WO2006018853A2 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008108630A1 (fr) * 2007-03-02 2008-09-12 Ultimorphix Technologies B.V. Formes polymorphes de l'efavirenz
WO2009011567A1 (fr) * 2007-07-16 2009-01-22 Ultimorphix Technologies B.V. Formes cristallines d'efavirenz
WO2011032634A1 (fr) 2009-09-16 2011-03-24 Archimica Gmbh Sels d'éfavirenz, leur procédé de préparation et de libération du sel
WO2010073254A3 (fr) * 2008-12-22 2011-12-08 Hetero Research Foundation Procédé pour la préparation d'un polymorphe de l'éfavirenz
EP2471783A1 (fr) 2010-12-23 2012-07-04 Esteve Química, S.A. Nouvelle forme polymorphe de l'éfavirenz
US8242267B2 (en) 2004-08-19 2012-08-14 Hetero Drugs Limited Polymorphs of efavirenz
WO2014000555A1 (fr) * 2012-06-25 2014-01-03 上海迪赛诺药业有限公司 Procédé de préparation de la forme cristalline i de l'éfavirenz
US9138412B2 (en) 2009-11-04 2015-09-22 Hetero Research Foundation Bioequivalent formulation of efavirenz

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009087679A2 (fr) * 2007-12-24 2009-07-16 Matrix Laboratories Limited Procédé de préparation de formes polymorphes de (s)-6-chloro-(cyclopropyléthynyl)-1,4-dihydro-4-(trifluorométhyl)-2h-3,1-benzoxazin-2-one

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5663169A (en) * 1992-08-07 1997-09-02 Merck & Co., Inc. Benzoxazinones as inhibitors of HIV reverse transcriptase
DE69841972D1 (de) * 1997-02-05 2010-12-09 Merck Sharp & Dohme Verfahren zur kristallisation eines reverstranskriptase-inhibitors, bei welchem ein anti-lösungsmittel benutzt wird
US5965729A (en) * 1997-02-05 1999-10-12 Merck & Co., Inc. Process for the crystallization of a reverse transcriptase inhibitor using an anti-solvent
HRP990182A2 (en) 1998-06-11 2000-02-29 Du Pont Pharm Co Crystalline efavirenz
US6673372B1 (en) * 1998-06-11 2004-01-06 Bristol-Myers Squibb Pharma Company Crystalline Efavirenz
WO2000000475A1 (fr) * 1998-06-30 2000-01-06 Du Pont Pharmaceuticals Company Quinoline-2(1h)-ones substituees utiles comme inhibiteurs de la transcriptase inverse du vih
GB0006133D0 (en) 2000-03-14 2000-05-03 Smithkline Beecham Plc Novel pharmaceutical
US6992219B2 (en) * 2002-08-09 2006-01-31 Cephalon France Modafinil polymorphic forms
US7612098B2 (en) 2002-08-30 2009-11-03 Dr. Reddy's Laboratories Limited Amorphous hydrous esomeprazole magnesium
GB0321256D0 (en) 2003-09-11 2003-10-08 Generics Uk Ltd Novel crystalline compounds
WO2006018853A2 (fr) 2004-08-19 2006-02-23 Hetero Drugs Limited Nouveaux polymorphes d'efavirenz
WO2008002683A2 (fr) 2006-06-28 2008-01-03 Teva Pharmaceutical Industries Ltd. Carvédilol phosphate
EP1880714A1 (fr) 2006-07-20 2008-01-23 Helm AG Aripiprazole amorphe et son procédé de préparation
EP2049504A4 (fr) 2006-08-07 2010-09-22 Stiefel Laboratories Composés cristallins antifongiques

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8242267B2 (en) 2004-08-19 2012-08-14 Hetero Drugs Limited Polymorphs of efavirenz
US8466279B2 (en) 2004-08-19 2013-06-18 Hetero Drugs Limited Polymorphs of efavirenz
WO2008108630A1 (fr) * 2007-03-02 2008-09-12 Ultimorphix Technologies B.V. Formes polymorphes de l'efavirenz
WO2009011567A1 (fr) * 2007-07-16 2009-01-22 Ultimorphix Technologies B.V. Formes cristallines d'efavirenz
WO2010073254A3 (fr) * 2008-12-22 2011-12-08 Hetero Research Foundation Procédé pour la préparation d'un polymorphe de l'éfavirenz
US8383811B2 (en) 2008-12-22 2013-02-26 Hetero Research Foundation Process for preparing efavirenz polymorph
WO2011032634A1 (fr) 2009-09-16 2011-03-24 Archimica Gmbh Sels d'éfavirenz, leur procédé de préparation et de libération du sel
DE102009041443A1 (de) 2009-09-16 2011-03-31 Archimica Gmbh Salze des 6-Chlor-4-(cyclopropylethinyl)-1,4-dihydro-4-(trifluormethyl)-2H-3,1-benzoxazin-2-ons und deren Synthese, Aufreinigung und Anwendung als Vorstufen für Efavirenz
US9138412B2 (en) 2009-11-04 2015-09-22 Hetero Research Foundation Bioequivalent formulation of efavirenz
EP2471783A1 (fr) 2010-12-23 2012-07-04 Esteve Química, S.A. Nouvelle forme polymorphe de l'éfavirenz
WO2014000555A1 (fr) * 2012-06-25 2014-01-03 上海迪赛诺药业有限公司 Procédé de préparation de la forme cristalline i de l'éfavirenz

Also Published As

Publication number Publication date
US20060235008A1 (en) 2006-10-19
US20120115857A1 (en) 2012-05-10
US8242267B2 (en) 2012-08-14
WO2006018853A3 (fr) 2008-04-10
US20120271047A1 (en) 2012-10-25
US8466279B2 (en) 2013-06-18

Similar Documents

Publication Publication Date Title
US8242267B2 (en) Polymorphs of efavirenz
EP1606262A1 (fr) Nouvelles formes cristallines d'aripiprazole
JPS59176282A (ja) 薬理活性を有する化合物の異性体、その製法及びそれを含む製薬組成物
AU645886B2 (en) Thiazolidine-2,4-dione derivative, salt thereof, and production of the same
AU8311691A (en) 4-alkylimidazole derivatives and anti-hypertensive use thereof
NZ242191A (en) Crystalline tiagabine hydrochloride monohydrate, preparation and pharmaceutical compositions thereof
DE60319980T2 (de) Xanthin-phosphodiesterase-v-hemmer polymorphe
US20100190982A1 (en) Process for the preparation of lamivudine form i
US20090233932A1 (en) Novel crystalline forms of lamotrigine
WO2013102741A1 (fr) Forme cristalline delta du sel d'arginine du périndopril, son procede de preparation, et les compositions pharmaceutiques qui la contiennent
US8138343B2 (en) Crystalline polymorph of 7-ethyl-10-hydroxycamptothecin
EP2367804B1 (fr) Procédé pour la préparation d'un polymorphe de l'éfavirenz
EP0718289B1 (fr) Nouveaux dérivés d'acide parabanique comme inhibiteurs d'aldose réductase
JPS62281860A (ja) アルキレンアミノアルキレン　ヘテロ原子基を有するジヒドロ−３，５−ジカルボキシレ−ト
WO2004076443A1 (fr) Forme amorphe de potassium de losartan
US20100104649A1 (en) Lercanidipine Hydrochloride Polymorphs and an Improved Process for Preparation of 1,1,N-Trimethyl-N-(3,3-Diphenylpropyl)-2-Aminoethyl Acetoacetate
GB2120251A (en) Dihydropyridines
CN112521380A (zh) 一种利伐沙班中间体a的合成方法及其在制备利伐沙班中的应用
WO2004099183A1 (fr) Nouvelles formes polymorphes de pantoprazole sodium
KR960007533B1 (ko) 티아졸리딘-2,4-디온 유도체, 이의 염 및 이의 제조방법
JP2011105649A (ja) アゼルニジピンの結晶
US20050154052A1 (en) Novel crystalline forms of (s)-citalopram oxalate
EP2303842A1 (fr) Procédé pour la fabrication de la forme v de la lercanidipine.hcl
EP1785411A1 (fr) Forme crystalline de proptriptyline hydrochloride
WO2012007952A1 (fr) Nouveau composé polymorphe du chlorhydrate d'irinotécan

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 1846/CHENP/2004

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: 2006235008

Country of ref document: US

Ref document number: 10568904

Country of ref document: US

AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWP Wipo information: published in national office

Ref document number: 10568904

Country of ref document: US

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase